What are the risks of using Selective Serotonin Reuptake Inhibitors (SSRIs) during pregnancy on neonatal transition?

Risks of SSRIs During Pregnancy on Neonatal Transition

SSRIs used during pregnancy can cause neonatal adaptation syndrome in approximately one-third of exposed newborns, with symptoms including crying, irritability, jitteriness, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia, and seizures that typically appear within hours to days after birth and usually resolve within 1-2 weeks. 1

Neonatal Adaptation Syndrome

• Neonatal adaptation syndrome occurs in approximately 30% of infants exposed to SSRIs in the third trimester 2
• Symptoms typically begin within hours to days after birth 1
• Most symptoms resolve spontaneously within 1-2 weeks, though in rare cases they may persist up to 4 weeks 1
• Common symptoms include:
  • Crying, irritability, jitteriness, and restlessness 1
  • Tremors and shivering 1
  • Poor sucking and feeding difficulties 1
  • Hypertonia or rigidity 1
  • Tachypnea or respiratory distress 1
  • Sleep disturbance 1
  • Hypoglycemia 1
  • Seizures (rare) 1

Pathophysiology of Neonatal Effects

• There is debate whether these symptoms represent serotonin syndrome (due to increased serotonin in the intersynaptic cleft) or SSRI withdrawal (due to relative hyposerotonergic state) 1
• In adults, serotonin syndrome is characterized by:
  • Changes in mental status (agitation, confusion) 1
  • Autonomic hyperactivity (fever, tachycardia, tachypnea) 1
  • Neuromuscular abnormalities (tremor, hyperreflexia, hypertonia) 1
• Serotonin withdrawal in adults manifests with anxiety, headache, nausea, fatigue, and low mood 1

Serious Complications

• In severely affected infants, pharmacological intervention may be required 1
• Some studies suggest a possible association between SSRI use during pregnancy and persistent pulmonary hypertension of the newborn (PPHN) 3, 4, 5
  • The number needed to harm for PPHN with late pregnancy SSRI exposure is approximately 286-351 3
• FDA labels for fluoxetine and sertraline note that neonates exposed to SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding 4, 5

Management Recommendations

• Infants exposed to SSRIs in utero should be monitored for at least 48 hours after birth 2, 6
• Arrange for early follow-up after hospital discharge for infants exposed to SSRIs in the third trimester 1, 7
• In severely affected infants, a short-term course of chlorpromazine has provided measurable relief of symptoms 1
• Most cases can be managed with supportive care and non-pharmacological measures 2

Risk-Benefit Considerations

• The American Academy of Pediatrics recommends that SSRI treatment should be continued during pregnancy at the lowest effective dose when clinically indicated 1, 7
• Untreated depression during pregnancy is associated with:
  • Premature birth 3, 7
  • Decreased initiation of breastfeeding 3, 7
  • Potential harmful effects on the mother-infant relationship 7
• Women who discontinue antidepressant medication during pregnancy show a significant increase in relapse of major depression 5

Specific SSRI Considerations

• Paroxetine and sertraline are considered to have more favorable profiles during breastfeeding due to lower infant-to-maternal plasma concentration ratios 1, 3
• Sertraline, paroxetine, and fluvoxamine are minimally excreted in human milk and provide the infant <10% of the maternal daily dose 1
• Fluoxetine and paroxetine have been associated with a small but higher risk for birth defects compared to other SSRIs 8

Clinical Approach

• Use the lowest effective dose of SSRI during pregnancy 3, 7
• Monitor for symptoms of depression throughout pregnancy 3, 7
• For women already taking SSRIs who become pregnant, continuation of treatment is generally recommended if clinically indicated 3, 5
• Inform pediatric providers about maternal SSRI use to ensure appropriate monitoring of the newborn 2, 6
• Monitor exposed newborns for at least 48 hours after birth for signs of neonatal adaptation syndrome 2, 6